The deafness (dn/dn) mutant mouse provides a valuable model of human congenital deafness. We investigated the properties of synaptic transmission in the anteroventral cochlear nucleus (AVCN) of normal and congenitally deaf dn/dn mice. Excitatory postsynaptic currents (EPSCs) were evoked by focal stimulation of single auditory nerve fibres, and measured by whole‐cell recordings from neurones in AVCN slices (mean postnatal age = P13). Absolute amplitudes of both AMPA‐ and NMDA‐mediated components of evoked EPSCs were greater (170 %) in deaf versus control animals. Enhanced transmission in deaf mice was due to a presynaptic mechanism. Variance‐mean analysis revealed that the probability of transmitter release was significantly greater in deaf (Pr= 0.8) versus control animals (Pr= 0.5). Following high frequency stimulation, deaf mice showed a greater depression of evoked EPSCs, and a significant increase in the frequency of delayed‐release (asynchronous) miniature EPSCs (aEPSCs) (deaf 100 Hz vs. control 7 Hz). The acetoxymethyl ester of EGTA (EGTA‐AM) blocked the increase in miniature aEPSCs and returned tetanic depression to control values. In deaf mice, reduction of mean Pr using cadmium caused an expected increase in paired‐pulse ratio (PPR). However, in the same cells, a similar reduction in release by EGTA‐AM did not result in a change in PPR, demonstrating that a change may occur in Pr without a concomitant change in PPR. In many respects, transmission in deaf mice was found to be remarkably similar to control mice, implying that many parameters of synaptic transmission develop normally in these animals. The two significant differences (higher Pr and asynchronous release in deaf mice) could both be reversed by the addition of EGTA‐AM, suggesting that endogenous calcium buffering may be impaired or undeveloped in the presynaptic terminals of the auditory nerve in deaf mice.

Most synaptic connections between individual neurons in the central nervous system involve multiple synaptic contacts. The number of contacts between a single presynaptic fibre and a postsynaptic neuron is often in the range of tens to hundreds, but at some synaptic connections may exceed one thousand . The strength of synaptic transmission at such multisynaptic connections is determined by the total number of synaptic contacts, the release probability at all of these contacts, and the postsynaptic response to transmitter release at all sites. Previous attempts to analyse the mechanisms underlying transmission at multisynaptic connections have been largely based on conventional quantal analysis, which has serious limitations, partly due to the complications of site-to-site nonuniformities in release probability and quantal postsynaptic current amplitude (Walmsley et al.

A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals (axonal varicosities) in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer (granule) and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus. These figures allow for numerous correlations with other quantitative parameters--cytological, biochemical, and pharmacological--of NA function in the hippocampus. They also provide a strong basis for elucidating, at a cellular level, the action of NA in this part of the brain.

Large calyceal synapses are often regarded as simple relay points, built for high-fidelity and high-frequency synaptic transmission and a minimal requirement for synaptic plasticity, but this view is oversimplified. Calyceal synapses can exhibit surprising activity-dependent developmental plasticity. Here we compare basal synaptic transmission and activity-dependent plasticity at two stereotypical calyceal synapses in the auditory pathway, the endbulb and the calyx of Held. Basal synaptic transmission was more powerful at the calyx than the endbulb synapse: the amplitude of evoked AMPA receptor-mediated excitatory postsynaptic currents (eEPSCs) was significantly greater at the calyx, as were the release probability, and the number of release sites. The quantal amplitude was smaller at the calyx, consistent with the smaller amplitude of spontaneous miniature EPSCs at this synapse. High-frequency trains of stimuli revealed that the calyx had a larger readily releasable pool of vesicles (RRP), less tetanic depression and less asynchronous transmitter release. Activity-dependent synaptic plasticity was assessed in congenitally deaf mutant mice (dn/dn). Previously we showed that a lack of synaptic activity in deaf mice increases synaptic strength at the endbulb of Held via presynaptic mechanisms. In contrast, we have now found that deafness does not affect synaptic transmission at the calyx synapse, as eEPSC and mEPSC amplitude, release probability, number of release sites, size of RRP, tetanic depression and asynchronous release were unchanged compared to normal mice. Synaptic transmission at the calyx synapse is more powerful and has less capacity for developmental plasticity compared to the endbulb synapse.